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Flt 1

Nghi C Nguyen, Melissa K Yee, Abuzar M Tuchayi, John M Kirkwood, Hussein Tawbi, James M Mountz
Introduction: This pilot study aimed at exploring the utility of the proliferation tracer F-18 fluorothymidine (FLT) and positron-emission tomography (PET)/magnetic resonance imaging (MRI) (FLT-PET/MRI) for early treatment monitoring in patients with melanoma brain metastasis (MBM) who undergo targeted therapy or immunotherapy. Material and Methods: Patients with newly diagnosed MBM underwent baseline and follow-up FLT-PET/MRI scans at 3-4 weeks of targeted therapy or immunotherapy...
2018: Frontiers in Oncology
Hinrich Wieder, Ambros J Beer, Jens Siveke, Tibor Schuster, Andreas K Buck, Ken Herrmann, Jens C Stollfuss
Purpose: The aim of this study was to correlate preoperative 3'-deoxy-3'-[18 F] fluorothymidine (FLT) uptake with the clinical outcome and survival in these patients after surgery. Materials and Methods: We performed a prospective analysis in 27 patients with adenocarcinoma of the pancreas (15 males, 12 females, mean age: 62 ± 13 years, range: 34 - 86 years). FLT PET (45 min p.i., 300 MBq FLT; ECAT HR+) images were acquired according to standard protocols. FLT uptake was quantified using standardised uptake values (SUV)...
February 9, 2018: Oncotarget
Susie Choi, Hironori Uehara, Yuanyuan Wu, Subrata Das, Xiaohui Zhang, Bonnie Archer, Lara Carroll, Balamurali Krishna Ambati
Short-activating RNA (saRNA), which targets gene promoters, has been shown to increase the target gene expression. In this study, we describe the use of an saRNA (Flt a-1) to target the flt-1 promoter, leading to upregulation of the soluble isoform of Flt-1 and inhibition of angiogenesis. We demonstrate that Flt a-1 increased sFlt-1 mRNA and protein levels, while reducing VEGF expression. This was associated with suppression of human umbilical vascular endothelial cell (HUVEC) proliferation and cell cycle arrest at the G0/G1 phase...
2018: PloS One
Bianca A Trombetta, Becky C Carlyle, Aaron M Koenig, Leslie M Shaw, John Q Trojanowski, David A Wolk, Joseph J Locascio, Steven E Arnold
OBJECTIVE: Alzheimer's disease (AD) is a complex neurodegenerative disease driven by multiple interacting pathophysiological processes that ultimately results in synaptic loss, neuronal death, and dementia. We implemented a fit-for-purpose modeled approach to qualify a broad selection of commercially available immunoassays and evaluate the biotemporal stability of analytes across five pathophysiological domains of interest in AD, including core amyloid-β (Aβ) and tau AD biomarkers, neurodegeneration, inflammation/immune modulation, neurovascular injury, and metabolism/oxidative stress...
2018: PloS One
Zhonglin Xiao, Songjun Li, Yan Yu, Mengxia Li, Jie Chen, Feng Wang, Jian Zhang, Weifen Deng, Qing Yang, Xiujun Fan
Studies have shown that sFlt-1 overproduction stimulated by excess VEGF of deciduous origin in trophoblasts can cause preeclampsia. However, the mechanism underlying how VEGF regulates sFtl-1 expression in trophoblasts remains unknown. To address this issue, JEG3 and HTR-8/SV neo (HTR8) trophoblast cell lines were used to investigate the signaling pathways involved in the regulation of sFlt-1 production via VEGF overexpression in vitro. JEG3 (VEGF-GFP-JEG3, V-J) and HTR8 (VEGF-GFP-HTR8, V-H) cells overexpressing VEGF165 were established by infecting the JEG3 and HTR8 cell lines with lentivirus expressing VEGF165...
March 1, 2018: Molecular and Cellular Biochemistry
Jimmy Ly, Noel S Ha, Shilin Cheung, R Michael van Dam
Miniaturized synthesis of positron emission tomography (PET) tracers is poised to offer numerous advantages including reduced tracer production costs and increased availability of diverse tracers. While many steps of the tracer production process have been miniaturized, there has been relatively little development of microscale systems for the quality control (QC) testing process that is required by regulatory agencies to ensure purity, identity, and biological safety of the radiotracer before use in human subjects...
February 22, 2018: Analytical and Bioanalytical Chemistry
Shyam S Chaurasia, Rayne R Lim, Bhav H Parikh, Yeo Sia Wey, Bo Bo Tun, Tien Yin Wong, Chi D Luu, Rupesh Agrawal, Arkasubhra Ghosh, Alessandra Mortellaro, Elizabeth Rackoczy, Rajiv R Mohan, Veluchamy A Barathi
Diabetic retinopathy (DR) is a retinal microvascular disease characterized by inflammatory and angiogenic pathways. In this study, we evaluated NLRP3 inflammasome in a double transgenic mouse model, Akimba (Ins2 Akita xVEGF +/- ), which demonstrates hyperglycemia, vascular hyperpermeability and neovascularization seen in the proliferative DR. Retinal structural integrity, vascular leakage and function were examined by fundus photography, fluorescein angiography, optical coherence tomography, retinal flat mounts, laser speckle flowgraphy (LSFG), and electroretinography in Akimba and its parental strains, Akita (Ins2 Akita ) and Kimba (trVEGF029) mice...
February 12, 2018: Scientific Reports
Linxiao Wang, Shan Xu, Xiaobo Liu, Xiuying Chen, Hehua Xiong, Shanshan Hou, Wensheng Zou, Qidong Tang, Pengwu Zheng, Wufu Zhu
Five series of N-methylpicolinamide moiety and thienopyrimidine moiety bearing triazole (21-26, 27-34, 35-41, 42-47 and 48-54) were designed and synthesized. And all the target compounds were evaluated for the IC50 values against three cancer cell lines (A549, HepG2 and MCF-7) and some selected compounds (43, 49 and 52) were further evaluated for the activity against c-Met, Flt-3, VEGFR-2, c-Kit and EGFR kinases. Moreover, SARs and docking studies indicated that thieno[3,2-d]pyrimidine bearing triazole moiety was privileged structure for the activity...
January 31, 2018: Bioorganic Chemistry
Katia Herz, Alexandra Becker, Chenyue Shi, Masatsugo Ema, Satoru Takahashi, Michael Potente, Michael Hesse, Bernd K Fleischmann, Daniela Wenzel
Endothelial cell proliferation is a key process during vascular growth but its kinetics could only be assessed in vitro or ex vivo so far. To enable the monitoring and quantification of cell cycle kinetics in vivo, we have generated transgenic mice expressing an eGFP-anillin construct under control of the endothelial-specific Flt-1 promoter. This construct labels the nuclei of endothelial cells in late G1, S and G2 phase and changes its localization during the different stages of M phase, thereby enabling the monitoring of EC proliferation and cytokinesis...
February 7, 2018: Angiogenesis
Michiko Yamashita, Keiichi Kumasawa, Hitomi Nakamura, Tadashi Kimura
INTRODUCTION: Placenta previa is an abnormality in which the placenta covers the internal uterine os, and it can cause serious morbidity and mortality in both mother and fetus due to catastrophic hemorrhage. Some pregnant women recover from placenta previa due to a phenomenon called "migration." However, the mechanism of "migration" of the placenta has not been elucidated. METHODS: Human placentas were collected from patients with placenta previa and those with no abnormal placentation (control)...
January 30, 2018: Biochemical and Biophysical Research Communications
Tadakazu Tokumura, Naoko Yoshida, Kanami Mori-Yasumoto, Osamu Shirota, Takuro Kurita
The apparent degradation rate constant of fluticasone propionate (FLT) in 0.1 M NaOH:methanol=1:1 at 37 °C was previously reported to be 0.169±0.003 h-1, and four degradation products (products 1-4) were observed in the solution. The aims of the present study were to assess the degradation rates of FLT in other alkaline solutions and clarify the chemical structures of the four degradation products in order to obtain basic data for designing an enema for inflammatory bowel disease. The apparent degradation rate constants in 0...
October 2017: Journal of Pharmaceutical Analysis
Hao Zhang, Yanling Tao, Saisai Ren, Haihui Liu, Hui Zhou, Jiangwei Hu, Yongyong Tang, Bin Zhang, Hu Chen
The human umbilical cord (UC) is usually discarded as biological waste. However, it has attracted interest as a source of cells including endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs), which have demonstrated enormous potential in regenerative medicine. The present study describes a convenient protocol that has been developed to sequentially extract these two cell types from a single UC. EPCs which had properties of progenitor cells were successfully isolated from the UC vein. These cells had cobble-shaped morphology and expressed Flt-1, KDR, VE-cadherin, von Willebrand factor and CD31 mRNA, in addition to CD73, CD105 and vascular endothelial growth factor receptor-2...
January 2018: Experimental and Therapeutic Medicine
Ahmed Salem, Hitesh Mistry, Alison Backen, Clare Hodgson, Pek Koh, Emma Dean, Lynsey Priest, Kate Haslett, Ioannis Trigonis, Alan Jackson, Marie-Claude Asselin, Caroline Dive, Andrew Renehan, Corinne Faivre-Finn, Fiona Blackhall
INTRODUCTION: There is an unmet need to develop noninvasive biomarkers to stratify patients in drug-radiotherapy trials. In this pilot study we investigated lung cancer radiotherapy response and toxicity blood biomarkers and correlated findings with tumor volume and proliferation imaging. PATIENTS AND METHODS: Blood samples were collected before and during (day 21) radiotherapy. Twenty-six cell-death, hypoxia, angiogenesis, inflammation, proliferation, invasion, and tumor-burden biomarkers were evaluated...
December 11, 2017: Clinical Lung Cancer
Thushari I Alahakoon, Weiyi Zhang, Susan Arbuckle, Kewei Zhang, Vincent Lee
AIM: To localize, quantify and compare angiogenic factors, vascular endothelial growth factor (VEGF), placental growth factor (PlGF), as well as their receptors fms-like tyrosine kinase receptor (Flt-1) and kinase insert domain receptor (KDR) in the placentas of normal pregnancy and complications of preeclampsia (PE), intrauterine fetal growth restriction (IUGR) and PE + IUGR. METHODS: In a prospective cross-sectional case-control study, 30 pregnant women between 24-40 weeks of gestation, were recruited into four clinical groups...
February 1, 2018: Journal of Obstetrics and Gynaecology Research
G M Kramer, Y Liu, A J de Langen, E P Jansma, I Trigonis, M-C Asselin, A Jackson, L Kenny, E O Aboagye, O S Hoekstra, R Boellaard
INTRODUCTION: 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) positron emission tomography (PET) provides a non-invasive method to assess cellular proliferation and response to antitumor therapy. Quantitative 18F-FLT uptake metrics are being used for evaluation of proliferative response in investigational setting, however multi-center repeatability needs to be established. The aim of this study was to determine the repeatability of 18F-FLT tumor uptake metrics by re-analyzing individual patient data from previously published reports using the same tumor segmentation method and repeatability metrics across cohorts...
January 23, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Victor H Gerbaudo, Joseph H Killoran, Chun K Kim, Jason L Hornick, Jonathan A Nowak, Peter C Enzinger, Harvey J Mamon
OBJECTIVE: The aim of this prospective pilot study was to investigate the potential of serial FLT-PET/CT compared to FDG-PET/CT to provide an early indication of esophageal cancer response to concurrent neoadjuvant chemoradiation therapy. METHODS: Five patients with biopsy-proven esophageal adenocarcinomas underwent neoadjuvant chemoradiation (Tx) prior to minimally invasive esophagectomy. The presence of residual tumor was classified histologically using the Mandard et al...
January 13, 2018: Annals of Nuclear Medicine
Wenhui Wang, Shan Xu, Yongli Duan, Xiaobo Liu, Xiaojing Li, Caolin Wang, Bingbing Zhao, Pengwu Zheng, Wufu Zhu
Two series of aromatic hydrazone derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety (7a-r, 8a-i, 12a-b, 13a-c, 16a-d and 17a-e) were designed, synthesized and evaluated for the IC50 values against four cancer cell lines (A549, HepG2, MCF-7and PC-3). Two selected compounds (7c and 17e) were further evaluated for the activity against c-Met, Flt-3, VEGFR-2 and EGFR kinases. The data indicated that targets compounds were selective for c-Met kinase. And the most promising compound 7c was further studied in terms of dose-dependent, time-dependent and cell apoptosis...
December 27, 2017: European Journal of Medicinal Chemistry
Ahamed Khan, Ankita Shrestha, Kashyap Bhuyan, Indu B Maiti, Nrisingha Dey
The promoter fragment described in this study can be employed for strong transgene expression under both biotic and abiotic stress conditions. Plant-infecting Caulimoviruses have evolved multiple regulatory mechanisms to address various environmental stimuli during the course of evolution. One such mechanism involves the retention of discrete stress responsive cis-elements which are required for their survival and host-specificity. Here we describe the characterization of a novel Caulimoviral promoter isolated from Horseradish Latent Virus (HRLV) and its regulation by multiple stress responsive Transcription factors (TFs) namely DREB1, AREB1 and TGA1a...
January 11, 2018: Plant Molecular Biology
Yin Zhao, YanFang Zheng, XiaoXia Liu, QingQing Luo, Di Wu, XiaoPing Liu, Li Zou
STUDY QUESTION: Is it possible to improve vascular remodeling by inhibiting the excessive expression of protease activated receptor 1 (PAR-1) in trophoblast of abnormal placenta? SUMMARY ANSWER: Inhibition of trophoblast PAR-1 overexpression may promote placental angiogenesis and vascular remodeling, offering an alternative therapeutic approach for preeclampsia. WHAT IS KNOWN ALREADY: PAR-1 is high-affinity receptor of thrombin. Thrombin increases sFlt-1 secretion in trophoblast via the activation of PAR-1...
January 9, 2018: Molecular Human Reproduction
Nicole Madfis, Zhiqiang Lin, Ashwath Kumar, Simone A Douglas, Manu O Platt, Yuhong Fan, Kara E McCloskey
A well-formed and robust vasculature is critical to the health of most organ systems in the body. However, the endothelial cells (ECs) forming the vasculature can exhibit a number of distinct functional subphenotypes like arterial or venous ECs, as well as angiogenic tip and stalk ECs. In this study, we investigate the in vitro differentiation of EC subphenotypes from embryonic stem cells (ESCs). Using our staged induction methods and chemically defined mediums, highly angiogenic EC subpopulations, as well as less proliferative and less migratory EC subpopulations, are derived...
March 1, 2018: Stem Cells and Development
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